Journal of Interferon & Cytokine ResearchVol. 38, No. 7 Research ReportsFree Access
Differential Expression of Immune Inhibitory Checkpoint Signatures on Antiviral and Inflammatory T Cell Populations in Chronic Hepatitis B
Helen Cooksley
, Antonio Riva
, Krum Katzarov
, Tanya Hadzhiolova-Lebeau
, Slava Pavlova
, Marieta Simonova
, Roger Williams
, and Shilpa Chokshi
Published Online:1 Jul 2018https://doi.org/10.1089/jir.2017.0109
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Abstract
Virus-specific T cells are critical in mediating the pathogenesis of hepatitis B virus (HBV) infection. Interferon gamma (IFNγ)-producing T cells are associated with resolution; in contrast, interleukin-17 (IL-17)-producing T cells are linked to exacerbation of liver inflammation and injury. Checkpoint receptors stringently regulate T cell functions, with their expression profiles varying on different T cell subsets. Blockade of checkpoint receptors may be an effective therapeutic strategy for chronic hepatitis B (CHB); however, blockade may also inadvertently exacerbate proinflammatory responses. In this study, we sought to determine the balance of inflammatory and antiviral T cells and determine their inhibitory receptor profile. The frequency of total and HBV antigen-specific Th17 and Tc17 cells was higher in CHB patients compared with healthy controls (HCs). Th17 and Tc17 cells in CHB patients had significantly lower expression of T cell immunoglobulin and mucin domain protein-3 (TIM-3) compared with HCs, with no difference in programmed death-1 (PD-1) or CD244 expression. Conversely, Th1 and Tc1 cells in CHB patients hyperexpressed PD-1 and CD244, while TIM-3 expression was comparable in both cohorts. During CHB, antiviral IFNγ T cells hyperexpress multiple immune inhibitory receptors driving their functional impairment. In contrast, inflammatory Th17/Tc17 cells hypoexpress TIM-3, but not PD-1 or CD244. Checkpoint inhibitors for CHB should target PD-1 or CD244 to allow restoration of IFNγ responses without affecting inflammatory IL-17 production. 作者: StephenW 时间: 2018-7-27 18:02